Obesity is has become a health concern of global proportion. The National Center for Health Statistics (NCHS) estimates that over 120 million Americans are overweight, including about 56% of the adult population. Of these, about 52 million are considered obese, as measured by a body mass index (BMI) of 30% or greater. In Europe, an estimated 77 million people are obese, as measured by the same standard. This problem is not limited to western nations, as many developing countries are reported to have obesity rates over 75% of the adult population.
Type II Diabetes is a significant factor in the obese. Type II diabetes is characterized by a gradual loss of insulin secretion and a progressive reduction in β-cell mass. Insulin resistance increases the demand for insulin. As the β-cell mass declines, the pancreas is unable to sustain the high insulin levels required to maintain normoglycemia.
Weight loss, diet alteration and exercise can improve glycemic control. Beyond these measures, medical therapy of diabetes is intended to control blood sugar within acceptable limits. Patients with diabetes have a wide a number of therapeutic approaches. Medications such as sulfonylureas, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors are available orally. Insulin can be injected or inhaled. Recently a new class of drugs, labeled incretin-mimetics, aimed at enhancing the incretin effect, has been introduced. Many of these drugs, e.g., exenatide, require injection. As effective as they are, however, patients with diabetes can be expected to remain on diabetic medications for their entire lives.
Surgical options exist for obese diabetics, including relatively invasive surgeries such as gastric bypass surgery and duodenal switch surgery, and less invasive surgeries referred to as gastric restriction surgeries. In both gastric bypass and duodenal switch surgery, the capacity of the stomach is significantly reduced and a portion of the small intestine is rerouted. However, the degree of malabsorption is greater in duodenal switch surgery than gastric bypass surgery. Gastric restriction surgeries differ from bypass techniques in that the stomach capacity is reduced but the intestine is left substantially intact.
Diabetes resolution occurs in 48-95% of post-surgical patients, depending on the specific surgery. Thus surgery offers the potential of achieving complete resolution of type II diabetes. This enables patients to stop diabetic medications and glucose self-monitoring entirely.
Gastric bypass procedures (RYGB) incur a great deal of morbidity and create a malabsorptive state in the patient by passing a large portion of the intestines. Diabetes resolution (dR) has been reported to occur in 84% of patients after gastric bypass surgery. Cummings, et al., Surgery for Obesity and Related Diseases 3:109-15 (2007).
Gastrointestinal sleeves have been implanted to line the stomach and/or a portion of the small intestines to reduce the absorptive capabilities of the small intestine and/or to reduce the volume in the stomach, by reducing the available volume to the tubular structure of the graft running there through. Although weight loss may be effective while these types of devices are properly functioning, there are complications with anchoring the device within the stomach/GI tract, as the stomach and GI tract function to break down things that enter into them and to move/transport them through. Accordingly, the integrity of the anchoring of the device, as well as the device itself may be compromised over time by the acids and actions of the stomach and GI tract.
A sleeve gastrectomy is an operation in which the left side of the stomach is surgically removed. This results in a much reduced stomach which is substantially tubular and may take on the shape of a banana. This procedure is associated with a high degree of morbidity, as a large portion of the stomach is surgically removed. Additionally, there are risks of complications such as dehiscence of the staple line where the staples are installed to close the surgical incisions where the portion of the stomach was removed. Further, the procedure is not reversible.
In the laparoscopic duodenal switch (also referred to as biliopancreatic diversion or BPD), the size of the stomach is reduced in similar manner to that performed in a sleeve gastrectomy. Additionally, approximately half of the small intestine is bypassed and the stomach is reconnected to the shortened small intestine. This procedure suffers from the same complications as the sleeve gastrectomy, and even greater morbidity is associated with this procedure due to the additional intestinal bypass that needs to be performed. Still further, complications associated with malabsorption may also present themselves. Diabetes resolution has been reported to occur in 95% of patients after duodenal switch surgery (BPD). This diabetes resolution may occur within days after RYGB and BPD, often even before significant weight loss has occurred.
Gastric reduction or restrictive techniques have also been attempted. Unlike bypass procedures, these techniques do not involve reduction of intestinal volume. Such reduction or restrictive techniques include inserting instruments trans-orally and reducing the volume of the stomach by stapling portions of it together. The LAPBAND™ is a band that, when placed, encircles the fundus-cardia junction and is inflatable to constrict the same. It does not reduce the volume of the stomach, but rather restricts passage of food into the stomach, the theory being that the patient will feel satiety with a much less volume of food than previously. Diabetes resolution has been reported to occur in only 48% of patients after gastric restriction surgery, such as adjustable gastric binding (i.e., the LAPBAND™). Cummings, et al., Surgery for Obesity and Related Diseases 3:109-15 (2007).